Generally, if an artificial material is implanted to fill a bone defect area in a living body, it will be wrapped by a fibrous membrane, and finally isolated from surrounding tissues. This phenomenon is caused by a biological reaction for self-protecting from foreign matters. Exceptionally, some materials can be joined directly to a surrounding bone without any formation of fibrous membranes. A typical material having such a property includes hydroxyapatite Ca10(PO4)6(OH)2 and tricalcium phosphate Ca3(PO4)2.
Recently, an artificial bone made of an organic/inorganic composite material based on the above bioceramics is being developed. For example, Japanese Patent Laid-Open Publication No. H07-101708 discloses an implant for artificial bones or artificial tooth roots, which is formed as a molded piece by adding 5 to 40 weight % of water to a composition powder containing an apatite powder having a crystal grain size of 0.5 μm or less and a biomolecular organic matter such as collagen and applying a pressure of 50 MPa or more to the composition powder maintained at a temperature of 0 to 200° C., wherein the Young's modulus of the implant is adjustable in the range of 2 GPa to 110 MPa.
The inventors developed an oriented apatite/collagen composite material excellent in flexural strength, Young's modulus and compressive strength suitable as a biomedical bone-replaceable bone-reconstruction material having a bone-induction ability and a bone-conduction ability, through a method in which a phosphoric-acid solution containing collagen and a solution containing calcium salt are simultaneously dropped into a reaction vessel to coprecipitate calcium phosphate and collagen, and the obtained precipitate is shaped under pressure (Japanese Patent Laid-Open Publication No. H11-199209, J. BIOMEDICALS RESEARCH, 54: 445-453, Published online, 4 Dec. 2000).
Japanese Patent Laid-Open Publication No. H08-336584 discloses an apatite porous body for artificial bone marrows, which includes 30 weight % or more of apatite crystal particles having a particle size of 2 nm to 0.2 μm and an organic matter such as collagen, and has a through-hole with a diameter of 10 μm to 2 mm. Japanese Patent Laid-Open Publication No. H07-88174 discloses a compression-molded osteogenic implant comprising rhBPM (Bone Morphogenetic Protein) and a carrier therefor, wherein the osteogenic implant is formed in a support made of a bioceramics material.
As a substitute for a conventional bone-connecting metal plate or screw which has been generally used to fix, aid and restore a broken bone, a fusion-molded or extrusion-molded body made of polylactic acid as a biodecomposable/bioabsorbable material and formed in a rod, plate, screw or pin shape (Japanese Patent Laid-Open Publication Nos. H03-29663 and H05-168647).
While an autologous bone has been extracted and used as an implant for filling a bone defect area of a vertebral body in many cases, various kinds of artificial implants made of metal or ceramic have also been developed.
Since a vertical load is imposed on an artificial implant during use, the artificial implant must adequately satisfy requirements of flexural strength, flexural modulus and compressive strength, and have characteristics equivalent to those of an autologous bone.
For example, Japanese Patent Laid-Open Publication No. H04-303444 (Publication-1) discloses an artificial intervertebral disk in block form having various shapes. The artificial intervertebral disk comprises a plurality of porous bodies made of metal or ceramic, and a block made of polyvinyl alcohol hydrogel and integrally disposed between the porous bodies.
The specification and drawings of U.S. Pat. No. 5,702,449 (Publication-2) discloses an artificial vertebra comprising a load support member composed of a cylindrical metal sleeve with a sidewall having a number of apertures, and a bioceramic, such as hydroxyapatite/tricalcium phosphate, received in the inner space of the support member.
Japanese Patent Laid-Open Publication No. H10-33656 (Publication-3) discloses a vertebral-body fusion member in block form having various shapes. The vertebral-body fusion member comprises a porous body and a dense body having a mechanical strength which are made of β-tricalcium phosphate (TCP) as a bioabsorbable material having a bone-conduction ability, wherein the porous and dense bodies are integrally combined so that the dense body maintains an initial strength, and the porous body is gradually transformed into an autologous bone.
Japanese Patent Laid-Open Publication No. H11-513590 (Publication-4) discloses a porous biodecomposable matrix for bone replacement in spinal fusion, filling of bone defects, repair of broken bones or filling of periodontal defects. The matrix includes a network of insoluble biopolymer fiber (fibril collagen), binder, and fixed calcium phosphate mineral (hydroxyapatite) which are linked together. Publication-4 also discloses that it is desired to arrange the weight ratio of collagen to calcium phosphate mineral in the range of 8:2 to 1:1, to cross-link the matrix with glutalaldehyde or the like, and to include a bone marrow cell, an autologous bone and a bone growth factor.
Published Japanese Translation of PCT International Publication for Patent Application No. 2000-507484 (Publication-5) discloses a vertebral-column spacer comprising a load support member which includes a bone implant having a bioceramics matrix and a bone-growth stimulating component impregnated in the bioceramics matrix
Published Japanese Translation of PCT International Publication for Patent Application No. 2000-508221 (Publication-6) discloses a cylindrical implant comprising a matrix body which has fine pores and includes a biphasic calcium phosphate ceramic containing 2 to 40 volume % of hydroxyapatite (HAp) and 98 to 60 volume % of tricalcium phosphate (TCp), and a bone-growth inducing factor (TGF-β, BMP, prostaglandin etc.) captured in the matrix body. Publication-6 also discloses that the ceramic has fine pores with a size of about 200 to 600 μm, and the porosity rate of the ceramic is in the range of about 60 to 80%.
Published Japanese Translation of PCT International Publication for Patent Application No. 2000-517221 (Publication-7) discloses a prismatic or cylindrical intervertebral implant made of a conventional ceramic material having a maximum porosity of 30 volume %, wherein each of pores with a diameter of less than 100 μm is filled with air. Publication-7 also discloses that the intervertebral implant has a compressive strength of 400 to 600 MPa, and the ceramic material is transparent to X-ray.
The block disclosed in Publication-1 is simply implanted in a cortical bone, but no bone-marrow structure will be formed. The artificial vertebra disclosed in Publication-2 has a problem of causing rupture on the boundary between the bone and the implant under repetitive stress due to remanence of the metal sleeve which originally has no potential of becoming bone. Further, there is the risk of causing disruption of the implant itself due to early absorption/deprivation of TCP, and poor bone conduction ability provided only by HA left at the central region of the sleeve.
Publication-3 simply discloses that the dense body is combined with the porous body to compensate for a poor strength of β-tricalcium phosphate (TCP). The matrix disclosed in Publication-4 simply includes a mixture of collagen and apatite, which has neither a bone-like nanocomposite structure nor a self-organizing function. In addition, the matrix is insufficient in strength and bone-forming ability.
The matrix itself of the spacer disclosed in Publication-5 has no ability of forming bone marrow. The spacer also involves a conventional problem such as complications in a bone-extraction area and metal fatigue, due to use of an autologous bone and a metal component. Further, allogeneic bone transplantation involves the risk of AIDS or hepatitis infection. While the porous body disclosed in Publication-6 is made of a TCP-HAp composite material, it has no self-organizing function. Further, the implant itself is not a carrier directly absorbing BMP. While the porous body disclosed in Publication-7 has a high porosity, it involves the risk of rupture under repetitive stress due to insufficient transformation into an autologous bone. Further, any vertebra structure cannot be biologically formed without using a bone-marrow implant.
As mentioned above, each of the conventional artificial vertebrae is not a bioabsorbable material having abilities of bone-marrow formation and self-organization (bone-tissue regeneration).